scholarly journals Analog synthetic biology

2014 ◽  
Vol 372 (2012) ◽  
pp. 20130110 ◽  
Author(s):  
R. Sarpeshkar
Keyword(s):  
Synthetic Biology ◽  
Feedback Linearization ◽  
Dynamic Range ◽  
Analog Computation ◽  
Digital Computation ◽  
Use Of Resources ◽  
Time Space ◽  
Gene And Protein Expression ◽  
Pros And Cons ◽  
In Cells

We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations.

Analog Versus Digital: Extrapolating from Electronics to Neurobiology

1998 ◽  
Vol 10 (7) ◽  
pp. 1601-1638 ◽  
Author(s):  
Rahul Sarpeshkar
Keyword(s):  
Signal To Noise Ratio ◽  
Maximum Efficiency ◽  
Analog Computation ◽  
Hybrid Form ◽  
Digital Computation ◽  
Use Of Resources ◽  
Processing Resources ◽  
Pros And Cons ◽  
The Brain ◽  
Optimal Signal

We review the pros and cons of analog and digital computation. We propose that computation that is most efficient in its use of resources is neither analog computation nor digital computation but, rather, a mixture of the two forms. For maximum efficiency, the information and information-processing resources of the hybrid form must be distributed over many wires, with an optimal signal-to-noise ratio per wire. Our results suggest that it is likely that the brain computes in a hybrid fashion and that an underappreciated and important reason for the efficiency of the human brain, which consumes only 12 W, is the hybrid and distributed nature of its architecture.

scholarly journals Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Matthew Mannarino ◽  
Hosni Cherif ◽  
Li Li ◽  
Kai Sheng ◽  
Oded Rabau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Back Pain ◽  
Protein Expression ◽  
Disc Degeneration ◽  
Cell Senescence ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Synthesis ◽  
Gene And Protein Expression ◽  
Pain Patients ◽  
In Cells

Abstract Background There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. Methods Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). Results An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. Conclusions Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

scholarly journals Synthetic Biology Parts for the Storage of Increased Genetic Information in Cells

2017 ◽  
Vol 6 (10) ◽  
pp. 1834-1840 ◽  
Author(s):  
Sydney E. Morris ◽  
Aaron W. Feldman ◽  
Floyd E. Romesberg
Keyword(s):  
Synthetic Biology ◽  
Genetic Information ◽  
In Cells

scholarly journals Blueprints for Biosensors: Design, Limitations, and Applications

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 375 ◽  
Author(s):  
Alexander Carpenter ◽  
Ian Paulsen ◽  
Thomas Williams
Keyword(s):  
Transcription Factors ◽  
Synthetic Biology ◽  
Nucleic Acids ◽  
Dynamic Range ◽  
Optimal Performance ◽  
Ease Of Use ◽  
Ligand Specificity ◽  
Biotechnological Application ◽  
Wide Range ◽  
Output Time

Biosensors are enabling major advances in the field of analytics that are both facilitating and being facilitated by advances in synthetic biology. The ability of biosensors to rapidly and specifically detect a wide range of molecules makes them highly relevant to a range of industrial, medical, ecological, and scientific applications. Approaches to biosensor design are as diverse as their applications, with major biosensor classes including nucleic acids, proteins, and transcription factors. Each of these biosensor types has advantages and limitations based on the intended application, and the parameters that are required for optimal performance. Specifically, the choice of biosensor design must consider factors such as the ligand specificity, sensitivity, dynamic range, functional range, mode of output, time of activation, ease of use, and ease of engineering. This review discusses the rationale for designing the major classes of biosensor in the context of their limitations and assesses their suitability to different areas of biotechnological application.

scholarly journals Bioinspired genotype–phenotype linkages: mimicking cellular compartmentalization for the engineering of functional proteins

2015 ◽  
Vol 5 (4) ◽  
pp. 20150035 ◽  
Author(s):  
Liisa D. van Vliet ◽  
Pierre-Yves Colin ◽  
Florian Hollfelder
Keyword(s):  
Synthetic Biology ◽  
Directed Evolution ◽  
Enzyme Catalysis ◽  
Darwinian Evolution ◽  
Oil Droplets ◽  
Shell Beads ◽  
Cellular Compartmentalization ◽  
In Cells

The idea of compartmentalization of genotype and phenotype in cells is key for enabling Darwinian evolution. This contribution describes bioinspired systems that use in vitro compartments—water-in-oil droplets and gel-shell beads—for the directed evolution of functional proteins. Technologies based on these principles promise to provide easier access to protein-based therapeutics, reagents for processes involving enzyme catalysis, parts for synthetic biology and materials with biological components.

scholarly journals The Pros and Cons of Compressive Sensing for Wideband Signal Acquisition: Noise Folding versus Dynamic Range

2012 ◽  
Vol 60 (9) ◽  
pp. 4628-4642 ◽  
Author(s):  
Mark A. Davenport ◽  
Jason N. Laska ◽  
John R. Treichler ◽  
Richard G. Baraniuk
Keyword(s):  
Compressive Sensing ◽  
Dynamic Range ◽  
Signal Acquisition ◽  
Wideband Signal ◽  
Pros And Cons ◽  
Noise Folding

scholarly journals Eribulin rapidly inhibits TGF-β-induced Snail expression and can induce Slug expression in a Smad4-dependent manner

2019 ◽  
Vol 121 (7) ◽  
pp. 611-621
Author(s):  
Roma Kaul ◽  
April L. Risinger ◽  
Susan L. Mooberry
Keyword(s):  
Breast Cancer ◽  
Transcription Factors ◽  
Dependent Manner ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Microtubule Disruption ◽  
Microtubule Targeting Agents ◽  
Gene And Protein Expression ◽  
Slug Expression ◽  
In Cells

Abstract Background Evidence shows that the anticancer effects of microtubule targeting agents are not due solely to their antimitotic activities but also their ability to impair microtubule-dependent oncogenic signalling. Methods The effects of microtubule targeting agents on regulators of TGF-β-induced epithelial-to-mesenchymal transition (EMT) were evaluated in breast cancer cell lines using high content imaging, gene and protein expression, siRNA-mediated knockdown and chromatin immunoprecipitation. Results Microtubule targeting agents rapidly and differentially alter the expression of Snail and Slug, key EMT-promoting transcription factors in breast cancer. Eribulin, vinorelbine and in some cases, ixabepalone, but not paclitaxel, inhibited TGF-β-mediated Snail expression by impairing the microtubule-dependent nuclear localisation of Smad2/3. In contrast, eribulin and vinorelbine promoted a TGF-β-independent increase in Slug in cells with low Smad4. Mechanistically, microtubule depolymerisation induces c-Jun, which consequently increases Slug expression in cells with low Smad4. Conclusion These results identify a mechanism by which eribulin-mediated microtubule disruption could reverse EMT in preclinical models and in patients. Furthermore, high Smad4 levels could serve as a biomarker of this response. This study highlights that microtubule targeting drugs can exert distinct effects on the expression of EMT-regulating transcription factors and that identifying differences among these drugs could lead to their more rational use.

scholarly journals Optimized Protocol for the In Situ Derivatization of Glutathione with N-Ethylmaleimide in Cultured Cells and the Simultaneous Determination of Glutathione/Glutathione Disulfide Ratio by HPLC-UV-QTOF-MS

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 292
Author(s):  
Xueni Sun ◽  
Raffaela S. Berger ◽  
Paul Heinrich ◽  
Ibtissam Marchiq ◽  
Jacques Pouyssegur ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Limit Of Detection ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Internal Standard ◽  
Glutathione Disulfide ◽  
Optimized Protocol ◽  
In Situ Derivatization ◽  
In Cells

Glutathione (GSH) and glutathione disulfide (GSSG) are commonly used to assess the oxidative status of a biological system. Various protocols are available for the analysis of GSH and GSSG in biomedical specimens. In this study, we present an optimized protocol for the in situ derivatization of GSH with N-ethylmaleimide (NEM) to prevent GSH autooxidation, and thus to preserve the GSH/GSSG ratio during sample preparation. The protocol comprises the incubation of cells in NEM containing phosphate buffered saline (PBS), followed by metabolite extraction with 80% methanol. Further, to preserve the use of QTOF-MS, which may lack the linear dynamic range required for the simultaneous quantification of GSH and GSSG in non-targeted metabolomics, we combined liquid chromatographic separation with the online monitoring of UV absorbance of GS-NEM at 210 nm and the detection of GSSG and its corresponding stable isotope-labeled internal standard by QTOF-MS operated with a 10 Da Q1 window. The limit of detection (LOD) for GS-NEM was 7.81 µM and the linear range extended from 15.63 µM to 1000 µM with a squared correlation coefficient R2 of 0.9997. The LOD for GSSG was 0.001 µM, and the lower limit of quantification (LLOQ) was 0.01 µM, with the linear (R2 = 0.9994) range extending up to 10 µM. The method showed high repeatability with intra-run and inter-run coefficients of variation of 3.48% and 2.51% for GS-NEM, and 3.11% and 3.66% for GSSG, respectively. Mean recoveries of three different spike-in levels (low, medium, high) of GSSG and GS-NEM were above 92%. Finally, the method was applied to the determination of changes in the GSH/GSSG ratio either in response to oxidative stress in cells lacking one or both monocarboxylate transporters MCT1 and MCT4, or in adaptation to the NADPH (nicotinamide adenine dinucleotide phosphate) consuming production of D-2-hydroxyglutarate in cells carrying mutations in the isocitrate dehydrogenase genes IDH1 and IDH2.

High‐resolution velocity notch filter without Gibbs effect

Geophysics ◽  
1997 ◽  
Vol 62 (1) ◽  
pp. 274-287 ◽  
Author(s):  
Eugene Lichman ◽  
E. John Northwood
Keyword(s):  
Dynamic Range ◽  
Inverse Fourier Transform ◽  
Notch Filter ◽  
Seismic Profile ◽  
Energy Separation ◽  
Profile Data ◽  
Discrete Function ◽  
Spatial Aliasing ◽  
Time Space ◽  
A New Technique

A new technique has been developed to reject or pass constant velocity coherent energy. Compared to the widely used frequency‐wavenumber (ο‐k) filtering method, this technique does not show either spatial aliasing or Gibbs effect. The filter operator is designed analytically as an infinite continuous function in the ο‐k domain. This function has the property that, when transformed by the integral inverse Fourier transform into the time‐space (t‐x) domain, it becomes a short discrete function with the same properties as the continuous infinite function in the ο‐k domain. No sampling or truncation of the filter operator is needed, hence no Gibbs oscillations are introduced into the operator impulse response or into the filtered data. Because of the extremely high‐velocity resolution and dynamic range of the designed coherent energy filter, it is particularly useful for the up‐ and downgoing energy separation on the vertical seismic profile data and for the peg‐leg multiples attenuation.

scholarly journals Image Simulation for Mingantu Ultrawide Spectral Radioheliograph in the Decimetre Wave Range

2015 ◽  
Vol 32 ◽  
Author(s):  
Jing Du ◽  
Yihua Yan ◽  
Wei Wang ◽  
Donghao Liu
Keyword(s):  
Inner Mongolia ◽  
Dynamic Range ◽  
Signal To Noise Ratio ◽  
Frequency Resolution ◽  
The Sun ◽  
Image Simulation ◽  
Time Space ◽  
Wide Range ◽  
Wave Range ◽  
Imaging Performance

AbstractThe MUSER is a solar-dedicated radio interferometric array, which will observe the Sun over a wide range of radio frequencies (0.4–15 GHz), and make high time, space and frequency resolution images of the Sun simultaneously. MUSER is located in Mingantu Station in Inner Mongolia of China, which is about 400 kilometres away from Beijing. MUSER consists of two arrays: MUSER-I and MUSER-II. MUSER-I contains 40 antennas with 4.5-m aperture operating at 400 MHz to 2 GHz. MUSER-II contains 60 antennas with 2-m aperture operating at 2 to 15 GHz. Currently, MUSER has already been established and entered into the stage of test observation. This work is focus on the imaging performance of MUSER-I. This paper introduces MUSER-I briefly, presents the analysis of the array configurations, and evaluates the image quality mainly using the dynamic range, fidelity index, and the peak signal-to-noise ratio, also make some actual solar model simulations with CASA, the results will be shown below.

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